Low temperature anodic bonding method using focused energy for assembly of micromachined systems

ABSTRACT

A method for assembling a medicine delivery system ( 10 ) includes providing a substrate ( 16 ) with a plurality of compartments ( 18 ), filling the compartments ( 18 ) with medicine ( 34 ), covering the compartments ( 18 ) with a cap ( 24 ), heating the system ( 10 ) at a relatively low temperature, applying a voltage bias ( 56 ) across the substrate ( 16 ) and the cap ( 24 ), and applying focused energy ( 54 ) to the substrate ( 16 ) and/or the cap ( 24 ) to seal them together and create a vacuum in the compartments ( 18 ).

FIELD OF THE INVENTION

[0001] The present invention generally relates to bonding methods forassembly of micromachined systems. More particularly, the presentinvention relates to a low temperature anodic bonding method usingfocused energy for assembly of micromachined systems.

BACKGROUND OF THE INVENTION

[0002] Medicine delivery is an important aspect of medical treatment.The efficacy of many medicines is directly related to the way in whichthey are administered. Some therapies require that the medicine berepeatedly administered to the patient over a long period of time. Thismakes the selection of a proper medicine delivery method problematic.Patients often forget, are unwilling, or are unable to take theirmedication. Medicine delivery also becomes problematic when themedicines are too potent for systemic delivery. Therefore, attempts havebeen made to design and fabricate a delivery device that is capable ofthe controlled, periodic or continuous release of a wide variety ofmolecules including, but not limited to, drugs and other therapeutics.

[0003] Micro-electro-mechanical system (MEMS) technology integrateselectrical components and mechanical components on a common siliconsubstrate using microfabrication technology. Integrated circuit (IC)fabrication processes, such as photolithography processes and othermicroelectronic processes, form the electrical components. The ICfabrication processes typically use materials such as silicon, glass,and polymers. Micromachining processes, compatible with the ICprocesses, selectively etch away areas of the IC or add new structurallayers to the IC to form the mechanical components. The integration ofsilicon-based microelectronics with micromachining technology permitscomplete electromechanical systems to be fabricated on a single chip.Such single chip systems integrate the computational ability ofmicroelectronics with the mechanical sensing and control capabilities ofmicromachining to provide smart devices small enough to be implantedinside of a human or animal.

[0004] Examples of implantable medicine delivery systems suitable forfabrication using microelectro-mechanical system (MEMS) technology aredescribed in U.S. Pat. No. 5,366,454 (Currie, et al.), and U.S. Pat. No.6,123,861 (Santini, Jr., et al.). These patents are described asimprovements over non-MEMS type of electromechanical devices that arelarger and less reliable and controlled release polymeric devices,designed to provide medicine release over a period of time via diffusionof the medicine through the polymer and/or degradation of the polymerover the desired time period following administration to the patient.

[0005] U.S. Pat. No. 5,366,454 (Currie, et al.) discloses a medicationdispensing device for implantation into an animal or human body, andincluding a substrate having a plurality of compartments, a closuremember, a rupturable membrane and a membrane rupturing system. Eachcompartment has a charging opening for charging the compartment with adose of medicine and a delivery opening permitting delivery of themedicine. The closure member, made of silicon, is anodically bonded tothe substrate, also made of silicon, for sealing the charging openingsof the compartments. The membrane, made of silicon, may be integrallyformed with the substrate or anodically bonded to the substrate, alsomade of silicon, for sealing the delivery openings of the compartments.The membrane has a predetermined elastic deformation limit and apredetermined rupture point. A “V-shaped” groove is formed in themembrane to define a line of weakness to assist the rupture of themembrane. The membrane rupturing system associated with each compartmentruptures the membrane thereof in response to an electrical signal. Themembrane rupturing system includes a stress-inducing member maintainingthe membrane stressed to substantially the elastic deformation limitthereof, and a piezoelectric transducer responsive to the electricalsignal for applying to the membrane additional stress sufficient toexceed the rupture point of the membrane, thereby causing the membraneto rupture. Upon rupture of the membrane, body fluids are permitted toenter into the compartment for mixing with the medicine containedtherein so that the medicine is released in admixture with the bodyfluids through the delivery opening into the animal or human body. Thedevice further includes a control circuit connected to a power sourcefor supplying the electrical signal to a respective piezoelectrictransducer of each membrane rupturing system to activate the respectivepiezoelectric transducer. However, a biologically compatible polymericfilm covers the membrane to bind any broken membrane fragments to thedevice and to prevent the fragments from being released into the humanor animal.

[0006] U.S. Pat. No. 6,123,861 (Santini, Jr., et al.) discloses amicrochip drug delivery device for controlling the rate and time ofdelivery of molecules, such as medicines, in either a periodic orcontinuous manner. This device typically includes hundreds to thousandsof reservoirs, or wells, formed in a silicon substrate containing themolecules and a release element that controls the rate of release of themolecules. The reservoirs can contain multiple medicines or othermolecules in variable dosages. The filled reservoirs can be capped withmaterials that passively disintegrate, materials that allow themolecules to diffuse passively out of the reservoir over time, ormaterials that disintegrate upon application of an electric potential.Release from an active device can be controlled by a preprogrammedmicroprocessor, remote control, or by biosensors.

[0007] Several methods are used to bond silicon wafers together or toother substrates, such as glass substrates, to form larger or morecomplex micromachined systems, such as medicine delivery systems,including: adhesion bonding, anodic bonding, eutectic bonding,glass-frit bonding, fusion bonding, low temperature fusion bonding, andmicrowave bonding. Among these various bonding methods engineeringtradeoffs exist for the applied temperature, applied voltage, appliedpressure, applied energy, bonding time, bond strength, material cost,etc.

[0008] Adhesion bonding uses an adhesive to bond the substratestogether. This is typically done by spin coating a thin film of adhesiveon one or both substrates before they are brought into contact. Thesubstrates are typically baked at a prescribed temperature to cure theadhesive.

[0009] Anodic bonding, otherwise known as electrostatic bonding,typically hermetically and permanently joins glass to silicon substrateswithout using adhesives. The glass substrate contains typically has ahigh percentage of alkali metals, such as sodium oxide. The silicon andglass substrates are brought into contact with each other. The siliconand glass substrates are heated to a temperature (typically in the range300-500° C. depending on the glass type) above the softening point ofthe glass substrate that results in the sodium oxide splitting up intosodium and oxygen ions. A high DC voltage (e.g., up to 1 kV) is appliedacross the substrates creating an electrical field that penetrates thesubstrates. The electric field causes the sodium ions to migrate fromthe interface between the substrates towards the cathode where they areneutralized providing a depletion layer with high electric fieldstrength. The resulting electrostatic attraction at the depletion layerbrings the silicon and glass into intimate contact. The electric fieldalso causes the oxygen ions to flow from the glass substrate to thesilicon substrate resulting in an anodic reaction at the interface withthe silicon ions in the silicon substrate to form irreversiblesilicon-oxygen-silicon bonds. The result is that the glass substrate isbonded to the silicon substrate with a permanent chemical bond. Thedisadvantages of anodic bonding include the relatively high temperaturerequired, temperature non-uniformity during vacuum sealing, andrelatively long bond times (e.g., 10 minutes).

[0010] Eutectic bonding and glass-frit bonding use a film of metal andglass ceramic adhesive, respectively, to hermetically seal thesubstrates together under high temperature.

[0011] Fusion bonding uses two silicon substrates having hydrophobic orhydrophilic, mirror-polished, flat and clean surfaces. The two surfacesof the substrates contact each other under high pressure creating atomicattraction forces that bond the two substrates together. The atomicattraction forces are strong enough to allow the bonded substrates to bemoved to a furnace. The bonded substrates are annealed at hightemperature (e.g., 900° C.-1100° C.) in the furnace to form a solidhermetic seal between the two substrates.

[0012] Low temperature fusion bonding advances the glass-frit bondingprocess. In contrast to the glass-frit bonding process, low temperaturefusion bonding does not use a glass ceramic adhesive to bond thesubstrates together. The low temperature fusion bonding process uses lowheat to soften the substrates, and pressure to squeeze and hold thesubstrates together until they bond over a prescribed period of time.

[0013] Microwave bonding uses electromagnetic energy to bond twometallized dielectric or silicon substrates to each other. Theelectromagnetic energy in the form of a pulse heats the metallicinterface between the two substrates to melt the interface togetherwhile permitting the substrates to remain cool.

[0014] It would be desirable to have a medicine delivery system, adaptedto be implanted in a human or animal, that actively releases a drug orother molecule into the animal or human by rupturing a membrane, withoutpermitting the ruptured membrane to separate from the medicine deliverysystem and to be released in the animal or human. Such a system wouldnot permit disintegrated membrane material to separate from the drugdelivery device and to be released in the animal or human, as disclosedin U.S. Pat. No. 6,123,861 (Santini, Jr., et al.). Further, such asystem would not require the biologically compatible polymeric filmshown as necessary by U.S. Pat. No. 5,366,454 (Currie, et al.) to bindany broken membrane fragments to the device and to prevent the fragmentsfrom being released into the human or animal.

[0015] It would also be desirable to have a bonding process tohermetically seal two substrates together at a temperature lower thanthe 300-500° C. range used for anodic bonding. Such a bonding processwould not damage thermally degraded materials, like the medicine in themedication dispensing device disclosed in U.S. Pat. No. 5,366,454(Currie, et al.). Such a bonding process would also be fast to providehigh manufacturing throughput. Further, such a process would also applya relatively low pressure to the substrates.

SUMMARY OF THE INVENTION

[0016] According to one aspect of the present invention, a bondingprocess seals two substrates together at a relatively low temperature.

[0017] According to another aspect of the present invention, the bondingprocess seals the two substrates together at a relatively low voltage.

[0018] According to another aspect of the present invention, the bondingprocess seals the two substrates together at a relatively low pressure.

[0019] According to another aspect of the present invention, the bondingprocess seals the two substrates together at a relatively high speed.

[0020] According to another aspect of the present invention, the bondingprocess hermetically and vacuum seals the two substrates together.

[0021] According to another aspect of the present invention, the bondingprocess seals the two substrates together using a combination of anodicbonding and focused energy bonding.

[0022] According to another aspect of the present invention, a methodbonds substrates in a micromachined system. A first substrate and asecond substrate are provided. The first substrate is placed in contactwith the second substrate. Heat is applied to the micromachined system.A bias voltage bias is applied across the first substrate and the secondsubstrate. Focused energy is applied to at least one of the firstsubstrate and the second substrate to seal the first substrate to thesecond substrate.

[0023] These and other aspects of the present invention are furtherdescribed with reference to the following detailed description and theaccompanying figures, wherein the same reference numbers are assigned tothe same features or elements illustrated in different figures. Notethat the figures may not be drawn to scale. Further, there may be otherembodiments of the present invention explicitly or implicitly describedin the specification that are not specifically illustrated in thefigures and vice versa.

BRIEF DESCRIPTION OF THE DRAWINGS

[0024]FIG. 1 illustrates a perspective view of a medicine deliverysystem, including a control unit and a plurality of medicine deliveryunits, in accordance with a preferred embodiment of the presentinvention.

[0025]FIG. 2 illustrates a magnified partial top plan view of themedicine delivery system of FIG. 1.

[0026]FIG. 3 illustrates a magnified top plan view of a medicinedelivery unit, as shown in FIGS. 1 and 2, having a release elementdisposed on a membrane.

[0027]FIG. 4 illustrates a magnified lateral cross-sectional view of themedicine delivery unit taken along line 4-4 in FIG. 3.

[0028]FIG. 5 illustrates a longitudinal cross-sectional view of themedicine delivery unit taken along line 5-5 in FIG. 3, before themembrane is ruptured.

[0029]FIG. 6 is a longitudinal cross-sectional view similar to FIG. 5but shows the medicine delivery unit after the membrane is ruptured.

[0030] FIGS. 7A-7K illustrate, in a sequence of steps, a MEMSfabrication process for making the medicine delivery unit, as shown inFIGS. 1-6, in accordance with the preferred embodiment of the presentinvention.

[0031]FIG. 8 illustrates a flowchart describing a method for sealing themedicine delivery unit, as shown in FIGS. 1-6, in accordance with thepreferred embodiment of the present invention.

[0032]FIG. 9 illustrates a block diagram of the control unit and themedicine delivery units, as shown in FIGS. 1 and 2, in accordance withthe preferred embodiment of the present invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0033]FIG. 1 illustrates a perspective view of a medicine deliverysystem 10, including a control unit 12 and a plurality of spaced-apartmedicine delivery units 14, in accordance with a preferred embodiment ofthe present invention. The medicine delivery system 10 is fabricatedusing the MEMS technology, as described above, using methods commonlyapplied to the manufacture of integrated circuits such as ultraviolet(UV) photolithography, reactive ion etching, and electron beamevaporation, as are well known in the art. The MEMS technologyfabrication procedure permits the manufacture of medicine deliverysystems 10 with primary dimensions (length of a side if square orrectangular, or diameter if circular) ranging from less than amillimeter to several centimeters. The thickness of a typical medicinedelivery system 10 is 300 micrometers, but can vary from approximately10 micrometers to several millimeters, depending on the system'sapplication. Changing the system thickness affects the maximum number ofmedicine delivery units 14 that may be incorporated into the system andthe volume of each medicine delivery unit 14. “In body” applications ofthe device would typically require systems having a primary dimension of2 cm or smaller. Systems for in body applications are small enough to beswallowed or implanted using minimally invasive procedures. Smaller inbody systems (on the order of a millimeter) can be implanted using acatheter or other injection means.

[0034] Preferably, the medicine delivery system 10 has a smallwafer-like substrate 16 providing the plurality of spaced-apart medicinedelivery units 14. The substrate 16 serves as a support for the medicinedelivery device 10. The substrate 16 may be any material that issuitable for etching or machining, for providing a support, and isimpermeable to medicines and to surrounding body fluids, such as, water,blood, electrolytes or other solutions. Examples of materials, suitablefor the substrate 16, include, without limitation, ceramics,semiconductors, glass, and degradable and non-degradable polymers.

[0035] Biocompatibility of the substrate material is preferred, but notrequired. For in body applications, non-biocompatible materials may beencapsulated in a biocompatible material, such as poly(ethylene glycol)or polytetrafluoroethylene-like materials, before use. Silicon is anexample of a material that forms a strong, non-degradable, easily etchedsubstrate that is impermeable to the enclosed medicines and thesurrounding body fluids. Poly(anhydride-co-imide) is an example of amaterial that forms a strong substrate that degrades or dissolves over aperiod of time into biocompatible components. This material is preferredfor in body applications where the system is implanted and physicalremoval of the device at a later time is not feasible or recommended.

[0036] Each medicine delivery unit 14 has a compartment 18, adapted tocontain or enclose a medicine 34 (shown in FIGS. 4-7), which is definedby a cavity, a recess, or a reservoir formed in the substrate 16 byetching, machining, or other known process. The compartments 18 are eachprovided with a charging opening 20 permitting receipt of medicine 34 inthe compartment 18, and with a delivery opening 22 permitting deliveryof the medicine contained therein. A cap 24 seals the charging openings20, preferably using a bonding method described in FIG. 8, or awaterproof epoxy or other appropriate material impervious to thesurrounding fluids. A membrane 26 seals the delivery openings 22.

[0037] As best seen in FIG. 4, the medicine 34 is inserted into thecharging opening 20 of the compartment 18 by any method including,without limitation, injection, inkjet printing, spin coating, capillaryaction, pulling or pushing the medicine using a vacuum or other pressuremechanism, melting the material into the compartment 18, centrifugationand related processes, packing solids into the compartment 18, or anycombination of these or other similar filling techniques.

[0038] The medicine 34 may be a solid, liquid or gel in the compartments18. Preferably, the medicine 34 is formed as a solid because the solidmedicine has a high concentration per unit volume, such as for examplein the pico-gram range. The medicine 34 may be any natural, synthetic,or semi-synthetic compound or mixture thereof that can be delivered. Inone embodiment, the medicine delivery system 10 is used to delivermedicines systemically to a patient in need thereof. In anotherembodiment, the construction and placement of the medicine deliverysystem 10 in a patient enables the localized release of medicines 34that may be too potent for systemic delivery. As used herein, medicinesare compounds or salts, prodrugs, solvates, salts and/or solvates ofprodrugs thereof, including, without limitation, proteins, nucleicacids, polysaccharides and synthetic organic molecules, having abioactive effect, for example, anesthetics, vaccines, chemotherapeuticagents, hormones, metabolites, sugars, immunomodulators, antioxidants,ion channel regulators, and antibiotics. The medicines 34 can be in theform of a single medicine or medicine mixtures and can includepharmaceutically acceptable carriers. In another embodiment, moleculesare released in body in any system where the controlled release of asmall (milligram to nanogram) amount of one or more molecules isrequired, for example, in the fields of analytic chemistry or medicaldiagnostics. Molecules can be effective as pH buffering agents,diagnostic agents, and reagents in complex reactions such as thepolymerase chain reaction or other nucleic acid amplificationprocedures.

[0039] Each compartment 18 may contain different medicines 34 dependingon the medical needs of the patient or other requirements of themedicine delivery system 10. For applications in medicine delivery, forexample, the medicines 34 in each of the rows can differ from eachother. Further, the rate of the release of the medicine 34 may differwithin each row to release a medicine at a fast rate from onecompartment 18 and a slow rate from another compartment 18. Eachcompartment 18 may also contain different dosages of the medicines 34.The dosages may also vary within each row of medicine delivery units 14.

[0040] For in body applications, the entire medicine delivery system 10,except for the side of the medicine delivery system 10 providing thedelivery openings 22 on the medicine delivery units 14, is encased in amaterial appropriate for the system 10. For in body applications, themedicine delivery system 10 is preferably encapsulated in abiocompatible material such as poly(ethylene glycol) orpolytetrafluoroethylene.

[0041] Use of MEMS technology fabrication techniques permit theincorporation of hundreds to thousands of compartments 18 in a singlemedicine delivery system 10. The spacing between each compartment 18depends on its particular application and whether or not the release ofthe medicine is active or passive. With an active release, the distancebetween the reservoirs may be slightly larger (between approximately 1and 10 micrometer) than with a passive release due to the space occupiedby a release element (not shown in FIG. 1) on or near each compartment18. The compartments 18 may be made in nearly any shape and depth, andneed not pass completely through the substrate 16. In a preferredembodiment, the compartments 18 are etched into a silicon substrate bypotassium hydroxide in the shape of a square pyramid, having side wallssloped at approximately fifty-four degrees, which pass completelythrough the substrate (approximately 300 micrometers) to the membrane 26on the other side of the substrate 16, as shown in FIG. 7. The pyramidalshape permits easy filling of the compartments 18 through the chargingopening 20 (approximately 500 micrometers by 500 micrometers) on apatterned side of the substrate 16, release through the delivery opening22 (approximately 50 micrometers by 50 micrometers) on the other side ofthe substrate 16, and provides a large cavity inside the medicinedelivery unit 14 for storing the medicine.

[0042] Referring next to FIGS. 2-6, FIG. 2 illustrates a magnifiedpartial top plan view of the medicine delivery system 10, of FIG. 1.FIG. 3 illustrates a magnified top plan view of a medicine delivery unit14, as shown in FIGS. 1 and 2, having a release element 28 disposed onthe membrane 26. FIG. 4 illustrates a magnified lateral cross-sectionalview of the medicine delivery unit 14, as shown in FIG. 3, having therelease element 28 disposed on the membrane 26. FIG. 5 illustrates alongitudinal elevation view of the medicine delivery unit 14, as shownin FIG. 3, before the membrane 26 is ruptured, in accordance with thepreferred embodiment of the present invention. FIG. 6 illustrates thelongitudinal elevation view of the medicine delivery unit 14, as shownin FIG. 3, after the membrane 26 is ruptured, in accordance with thepreferred embodiment of the present invention.

[0043] The release element 28 is associated with each medicine deliveryunit 14 for rupturing the membrane 26 in response to a control signal 78(shown in FIG. 9) from the control unit 12. The size, shape andplacement of the release element 28 may vary, depending on variousengineering considerations for the particular application. The releaseelement 28 is preferably disposed on the membrane 26, either insideand/or outside the compartment 18, using deposition techniques such aschemical vapor deposition, electron or ion beam evaporation, sputtering,spin coating, and other techniques known in the art. Various releaseelements may be used to rupture the membrane 26 including, withoutlimitation, electrostatic, magnetic, piezoelectric, bimorph, shapememory alloys, temperature, chemical, and other mechanisms that causestress or strain on the membrane 26.

[0044] When a temperature element such as a polysilicon piezoresistor isused as the release element 28 a thermal insulator, such as silicondioxide, may be used as the membrane 26 to isolate the temperatureelement from the medicine 34, if desired. The substrate 16 is preferablyformed of silicon and acts as a heat sink. The thermal conductivity forsilicon is 1.57 W/cm-degrees C., for silicon dioxide is 0.014W/cm-degrees C., and for polysilicon is 0.17 W/cm-degrees C. When thetemperature element 28 is heated, the membrane 26 cracks due to the highthermal gradient induced stresses on the membrane 26 causing themedicine delivery unit 14 to open. A thin film of tensile siliconnitride may be applied to the membrane 26 to assist in opening themedicine delivery unit 14 when the temperature element is heated. Afterthe membrane 26 is ruptured, the tensile silicon nitride pulls themembrane 26 back to assist in forming the delivery opening 22.

[0045] The release element 28 is electrically coupled to the controlunit 12 via electrodes 30 and 32. Exemplary conductive materials for theelectrodes include metals such as copper, gold, silver, and zinc andsome polymers. Typical film thickness of the electrodes 30 and 32 mayrange from 0.05 to several microns. When an electric potential isapplied to the electrodes 30 and 32, the membrane 26 ruptures along apredetermined pattern to expose the compartment 18 containing themedicine 34 to the surrounding fluids.

[0046] The predetermined rupture pattern preferably approximates thesize and shape of the release element 28. Preferably, the predeterminedrupture pattern has a width in the range of 2 to 20 micrometers, alength of a side of the delivery opening 22 in the range of 40 to 500micrometers, and spacing between the predetermined rupture pattern andthe edge of the delivery opening 22 in the range of 2 to 20 micrometers.

[0047] An insulating or dielectric material 40 such as silicon oxide(SiO₂) or silicon nitride (SiN₂) is deposited over the entire surface ofthe medicine delivery system 10 by methods such as chemical vapordeposition, electron or ion beam evaporation, sputtering, or spincoating and other techniques known in the art. Photoresist (not shown)is patterned on top of the dielectric material 40 to protect it frometching except on the release element 28 directly over each compartment18. The dielectric material 40 can be etched by plasma, ion beam, orchemical etching techniques. The purpose of this dielectric material 40and photoresist film is to protect the electrodes 30 and 32 fromcorrosion, degradation, or dissolution in all areas where electrode filmremoval is not necessary for release of the medicine 34.

[0048] The membrane 26 has a predetermined elastic deformation limit anda predetermined rupture point. The membrane 26 may be formed of avariety of materials including, without limitation, dielectric,polysilicon or silicon. The membrane 26 may have a line of weaknessformed therein along the predetermined rupture pattern to assist withrupturing the membrane 26. Preferably, the membrane 26 is thinner at theline of weakness than at other areas of the membrane 26. Such thinningmay be formed by a V-shaped indentation in the membrane 26. Preferably,the membrane 26 is integrally formed with the substrate 16.Alternatively, the membrane 26, can be formed separately from thesubstrate 16 and bonded thereto, such as with a membrane, formed ofsilicon, anodically bonded to a substrate 16, also formed of silicon.

[0049] Preferably, the membrane 26 is hermetically sealed over thedelivery openings 22 to form a vacuum in the compartments 18. Variousmechanisms for forming the vacuum seal include, without limitation, widearea heating mechanisms such as electrostatic bonding, and local areaheating sources such as laser, microwave, and infrared energy. The localarea heating mechanisms are preferred over the wide area heatingmechanisms because the local area heating mechanisms operate at a lowertemperature (e.g., 100-150 degrees C.) rather than at a highertemperature (e.g., 300-400 degrees C.). Using the lower temperature overthe local area prevents damage to the medicine delivery unit 10 and tothe medicine 34, and creates more strain on the membrane 26 due to thehigh temperature gradient along the membrane 26 from the local area tothe center of the membrane 26. In this case, each compartment 18 isdrawn under a vacuum causing the membrane 26 to be drawn inward into thecompartment 18 forming a concave shape. Under the vacuum, the membrane26 is strained to a point near to but less than the predeterminedelastic deformation limit and the predetermined rupture point of themembrane 26. Since the compartment 18 is under vacuum, the membrane 26is in a pre-stressed condition. The release element 28 causes themembrane 26 to bend past its yield point resulting the membrane 26rupturing along the predetermined pattern. Because the membrane 26 isalready in a pre-stressed state, the release element 28 does not requireas much energy to rupture the membrane 26, as compared to a membrane 26that is not in a pre-stressed state.

[0050] The membrane 26 has a first portion 35 located inside thepredetermined pattern and a second portion 37 located outside thepredetermined pattern. The first portion 35 of the membrane 26 isattached to the second portion 37 of the membrane 26 at a connectionarea 39. In the preferred embodiment of the present invention, the firstportion 35 of the membrane 26 forms a lid and the connection area 39forms a hinge 36. When the membrane 26 ruptures, the lid separates fromthe second portion 37 of the membrane 26, except at the hinge 36, topermit the medicine 34 to be delivered through the delivery opening 22,as shown in FIG. 6. The hinge 36 permits the lid to remain attached tothe medicine delivery system 10 so that it is not released in the animalor human. The first portion 35 of the membrane 26 and the connectionarea 39 may have various sizes, shapes and positions, depending onvarious engineering considerations for a particular application.

[0051] FIGS. 7A-7K illustrate, in a sequence of steps, a MEMSfabrication process for making the medicine delivery unit 14, as shownin FIGS. 1-6, in accordance with the preferred embodiment of the presentinvention. FIG. 7A illustrates the step of providing the substrate 16.FIG. 7B illustrates the substrate 16 having the membrane 26 applied toeach opposite side of the substrate 16. In FIG. 7C, material 38 for therelease element 28 is applied to the membrane 26 on one side of thesubstrate 16. In FIG. 7D, the material 38 for the release element 28 isselectively removed to form the release element 28. In FIG. 7B, theinsulator 40 is selectively applied to the membrane 26 and the membranematerial on the bottom side of the substrate 16 is selectively removed.In FIG. 7F, the medicine delivery unit 14 is turned over 180 degrees,either physically or for the sake of illustration. In FIG. 7G, thesubstrate 16 is etched or machined between the remaining portions of themembrane material to form the compartment 18 and the charging opening20. In FIG. 7H, the remaining portions of the membrane material areremoved. Alternatively, the remaining portions of the membrane materialstay depending on the type of material. In FIG. 7I, the compartment 18is filled with the medicine 34. In FIG. 7J, the cap 24 is disposed overthe compartment 18 to seal the charging opening 20 under vacuum,according to the method 60 described in FIG. 8. In FIG. 7K, the medicinedelivery unit 14 is again turned over 180 degrees, either physically orfor the sake of illustration.

[0052]FIG. 8 illustrates a flowchart describing a method 60 for sealingthe medicine delivery unit 10, as shown in FIGS. 7A-7K. The method 60starts at step 61. At step 62, the method 60 provides the substrate 16,having the compartments 18, and the cap 24 in an appropriate manner forhigh volume manufacturing. At step 63, the method 60 charges thecompartments 18 with the medicine 34, as describe above. At step 64, themethod 60 covers the compartments 18 with the cap 24, as describedabove. At step 65, the method 60 applies heat 58 to the medicinedelivery system 10. In the preferred embodiment of the present inventionthe heat is less than 100 degrees C., which is much less than the300-500 degrees C. temperature range used for traditional anodicbonding. At step 66, the method 60 applies a voltage bias 56 across thesubstrate 16 and the cap 24. Preferably, a positive voltage is appliedto the cap 24 and a negative voltage is applied to the substrate 16.Alternatively, the positive and negative voltages may be reversed,depending on the materials of the cap 24 and the substrate 16. In thepreferred embodiment of the present invention, the voltage bias 56 isgreater than 100 V and less than the 1 kV used for traditional anodicbonding. At step 67, the method 60 applies focused energy 54 to the cap24 to seal the cap 24 to the substrate 16 and to create a vacuum in thecompartments 18. The focused energy 54 includes, without limitation,microwave, laser, infrared, lamps, and the like. The focused energy 54couples into the cap 24 (e.g., at a wavelength less than 600 nm) toraise the temperature in a local area over one or more compartments 18for the duration of an energy pulse having a microsecond to millisecondtime duration. Such fast heat coupling assists in bonding the interfacebetween the cap 24 and the substrate 16, without damaging the cap 24,the substrate 16, or the medicine 34. Silicon material conducts heatquickly and glass material and a vacuum conducts heat slowly. Therefore,when the cap 24 is made of silicon and the substrate 16 is made ofglass, the focused energy 54 conducts slowly to the medicine 34. Notethat the focused energy 54 does not necessarily need to be aligned withparticular features of the medicine delivery system 10, depending on thesize of the features, the power level and time duration of the focusedenergy. At step 68, the method 60 ends. Although, the method 60describes a bonding process for assembly of the medicine delivery system10, the method may be used for any kind of micromachined system ordevice.

[0053] The benefits of the bonding process described in the method 60include: a fast manufacturing throughput, uniform seals, no damage tothe medicine 34, a low bonding temperature permitting more designflexibility and stable mechanical dimensions with temperature, a flatassembly process, no measurable flow of the glass material permittingsealing around previously machined grooves, cavities etc. without anyloss of dimensional tolerances, parasitic capacitances are keptextremely small because the glass material is an insulator, the bondingprocess may be performed in vacuum permitting hermetically sealedreference cavities to be formed, transparency of the glass at opticalwavelengths permits simple, but highly accurate, alignment ofpre-patterned glass and silicon wafers as well as to observe the insideof micro-fluidic devices, a high yield process that is tolerant toparticle contamination and wafer warp because the electrostatic fieldgenerates a high clamping force which overcomes surface irregularities,a low cost wafer scale process for first order packaging can be done ata chip level if required, multi-layer stacks permit easy routing tocomplex 3-D microstructures, and a high strength bond that is higherthan the fracture strength of the glass material.

[0054]FIG. 9 illustrates a block diagram of the control unit 12 and themedicine delivery units 14, as shown in FIGS. 1 and 2, in accordancewith the preferred embodiment of the present invention. The medicinedelivery system 10 accurately delivers medicine 34 at defined rates andtimes according to the needs of a human or animal patient or otherexperimental system. The control unit 12 includes a controller 70, amemory 72, a sensor 15, a power supply 74, and a demultiplexer 76.Preferably, the control unit 12 is constructed as an integrated circuit,but may be constructed as discrete circuits. The control unit 12 mayhave internal or external memory, such as RAM and/or ROM.

[0055] The power supply 74 provides power to the appropriate functionsin the control unit 12, such as the controller 70. Preferably, the powersupply 74 is a battery to permit portable or in body applications, andis preferably a thin film electrochemical cell deposited on thesubstrate 16. The criteria for selection of the power supply are smallsize, sufficient power capacity, ability to be integrated into thecontrol unit 12, and, in some applications, the ability to be rechargedand the length of time before recharging is necessary. Alternativebatteries of this type include lithium-based, rechargeablemicro-batteries that are typically only ten microns thick and occupy 1cm² of area. One or more of these batteries can be incorporated directlyinto the control unit 12.

[0056] The controller 70 generates the control signal 78 to control themedicine delivery units 14. The control signal 78 may be carried on asingle line carrying multiple signals, wherein each of the multiplesignals is associated with a corresponding medicine delivery unit 14.Alternatively, the control signal may be carried on a plurality oflines, wherein each of the plurality of lines is associated with eachmedicine delivery unit 14. Hence, the controller 70 in combination withthe control signal 78 actively controls the rupturing of the membrane 26for each medicine delivery unit 14.

[0057] The control unit 12 is designed based on the period over whichthe medicine delivery is desired, generally in the range of at leastthree to twelve months for in body applications. In contrast, releasetimes as short as a few seconds may be desirable for some applications.In some cases, continuous (constant) release from the compartment 18 maybe most useful. In other cases, a pulse (bulk) release from thecompartment 18 may provide more effective results. Note that a singlepulse medicine delivery from one compartment 18 can be transformed intoa multiple pulse medicine delivery by using multiple compartments 18. Inaddition, delivering several pulses of medicines in quick succession cansimulate continuous medicine delivery.

[0058] The controller 70 controls the time and rate of delivery of themedicine 34 from each compartment 18 responsive to a software program orcircuit, remote control, a signal from a sensor, or by any combinationof these methods. Preferably, the controller 70 is used in conjunctionwith the sensor 15, the memory 72, the power supply 74, and thedemultiplexer 76. The software program stored in the memory 72determines the time and rate of medicine delivery. The memory 72 sendsinstructions to the controller 70. When the time for release has beenreached as indicated by the software program, the controller 70 sendsthe control signal 78 corresponding to the address (location) of aparticular compartment 18 to the demultiplexer 76. The demultiplexer 76generates an electrical signal to the particular compartment 18addressed by the controller 70.

[0059] The sensor 15 advantageously provides a closed loop feedbacksystem to permit the medicine delivery system 10 to vary the time, rateand/or dosages of the medicine responsive to monitored conditions in theenvironment, such as the human or animal body.

[0060] The medicine delivery system 10 has numerous applications. Themedicine delivery system 10 can be used to deliver small, controlledamounts of chemical reagents or other molecules to solutions or reactionmixtures at precisely controlled times and rates. Analytical chemistryand medical diagnostics are examples of fields where the medicinedelivery system 10 can be used. The medicine delivery systems 10 can beimplanted into a patient, either by surgical techniques or by injection,or can be swallowed. The medicine delivery systems 10 provide deliveryof medicines to animals or persons who are unable to remember or beambulatory enough to take medication. The medicine delivery systems 10further provide delivery of many different medicines at varying ratesand at varying times of delivery.

[0061] Hence, while the present invention has been described withreference to various illustrative embodiments thereof, the presentinvention is not intended that the invention be limited to thesespecific embodiments. Those skilled in the art will recognize thatvariations, modifications and combinations of the disclosed subjectmatter can be made without departing from the spirit and scope of theinvention as set forth in the appended claims.

What is claimed is:
 1. A method for bonding substrates in amicromachined system, the method comprising the steps of: providing afirst substrate and a second substrate; placing the first substrate incontact with the second substrate; applying heat to the micromachinedsystem; applying a voltage bias across the first substrate and thesecond substrate; and applying focused energy to at least one of thefirst substrate and the second substrate to seal the first substrate tothe second substrate.
 2. The method according to claim 1, wherein thefirst substrate is made of glass and the second substrate is made ofsilicon.
 3. The method according to claim 1, wherein the heat is lessthan 100 degrees C.
 4. The method according to claim 1, wherein thevoltage bias is between 100 V and 1 kV.
 5. The method according to claim1, wherein the focused energy is provided by an energy source selectedfrom a group of energy sources consisting of a microwave, a laser, aninfrared, and a lamp source.
 6. The method according to claim 1, whereinthe focused energy has a wavelength less than 600 nm.
 7. The methodaccording to claim 1, wherein the micromachined system is a medicinedelivery system, wherein the first substrate includes a plurality ofcompartments each having charging openings for receiving medicine, andwherein the second substrate forms a cap that covers the chargingopenings.
 8. A method for assembling a medicine delivery system, themethod comprising the steps of: providing a substrate, having aplurality of compartments, and a cap; charging each of the plurality ofcompartments with medicine; covering the plurality of compartments withthe cap; applying heat to the medicine delivery system; applying avoltage bias across the substrate and the cap; and applying focusedenergy to at least one of the substrate and the cap to seal the cap tothe substrate and to create vacuum in the plurality of compartments. 9.The method according to claim 8, wherein the substrate is made of glassand the cap is made of silicon.
 10. The method according to claim 8,wherein the heat is less than 100 degrees C.
 11. The method according toclaim 8, wherein the voltage bias is between 100 V and 1 kV.
 12. Themethod according to claim 8, wherein the focused energy is provided byan energy source selected from a group of energy sources consisting of amicrowave, a laser, an infrared, and a lamp source.
 13. The methodaccording to claim 8, wherein the focused energy has a wavelength lessthan 600 nm.
 14. A method for assembling a medicine delivery system, themethod comprising the steps of: providing a substrate, having aplurality of compartments, and a cap, wherein the substrate is made ofglass and the cap is made of silicon; charging each of the plurality ofcompartments with medicine; covering the plurality of compartments withthe cap; applying heat to the medicine delivery system, wherein the heatis less than 100 degrees C.; applying a voltage bias across thesubstrate and the cap, wherein the voltage bias is between 100 V and 1kV; and applying focused energy, sourced from one of a microwave, alaser, an infrared, and a lamp source, to at least one of the substrateand the cap to seal the cap to the substrate and to create vacuum in theplurality of compartments, wherein the focused energy has a wavelengthless than 600 nm.